randomized open label phase ii study to evaluate the efficacy of enzalutamide in high risk male outpatients with covid-1

Conditions: COVID-19 Infection

Summary: high risk outpatient adult males with a confirmed sars-cov-2 infection will be included in the study. patients will be randomized to receive enzalutamide with standard of care (soc) or soc alone. enzalutamide will be administered daily p.o. from day 1 to day 28 or until confirmed negativization of nasopharyngeal swap (nps) polymerase chain reaction (pcr) (2 consecutive negative samples), whichever occurs first.


Eligibility criteria:
inclusion criteria: * documented covid-19 infection (confirmed by nps positive pcr for sars-cov-2) with mild symptoms not requiring hospitalization * first nps ≤4 days (96 hours) since onset of symptoms * randomization ≤72 hours since first nps * adult males aged ≥ 50 years * indication for outpatient treatment but at high risk for complications, at least 1 risk factor (age ≥ 65 years, hypertension, diabetes, cardiovascular disease, active malignancy, copd) * who performance status 0-1 * adequate hematologic values: haemoglobin ≥ 100 g/l, neutrophils ≥ 1.0 x 10(9)/l, platelets ≥ 150 x 10(9)/l. * adequate hepatic function: alt and ast ≤ 2.5 x uln, bilirubin ≤ 1.5 x uln (exception if gilbert's syndrome ≤ 2.5 x uln) * adequate renal function: calculated creatinine clearance ≥ 50 ml/min according to the formula of cockcroft-gault * patient is able to swallow the trial drugs and to comply with trial requirements * patient agrees not to father a child during participation in the trial and for 3 months thereafter exclusion criteria: * female sex * moderate to severe covid-19 symptoms requiring hospitalization * patients requiring inpatient treatment * concurrent antiviral drugs or ongoing interventional clinical trial or any off label drug for covid-19 * patients with ongoing prostate cancer treatment * clinically significant cardiovascular disease including: * myocardial infarction within 6 months prior to registration, * uncontrolled angina within 3 months prior to registration, * congestive heart failure nyha class iii or vi * qtc interval \> 480 ms * history of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes) * history of mobitz ii second or third degree heart block without a permanent pacemaker in place * uncontrolled hypertension as indicated by systolic blood pressure \> 170 mmhg or diastolic blood pressure \> 105 mmhg * deep venous thrombosis or pulmonary embolism within 6 months * history of cerebrovascular disease * severe concurrent disease, infection or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrolment. * known history of hiv, hepatitis b, hepatitis c * known history of seizures or any conditions that may predispose to seizure. history of loss of consciousness or ischemic cerebrovascular attack within 12 months prior to registration * concurrent anticoagulation with rivaroxaban or warfarin. concomitant and continuous use of systemic corticosteroids exceeding 10 mg/day of prednisone or a dose equivalent corticosteroid within 14 days before registration. * known hypersensitivity to enzalutamide or hypersensitivity to any of its components * any concomitant drugs contraindicated for use with enzalutamide according to the swissmedic approved product information * any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow-up.